ES2276768T3 - METHOD AND APPARATUS FOR BLOWING MOLD POLY CAPSULES (VINYL ALCOHOL) AND POLY CAPSULES (VINYL ALCOHOL) MOLDED BY BLOWING. - Google Patents

Abstract

A capsule is formed from a PVA composition by blow moulding. Such capsules can at last provide a viable alternative to gelatin for bio-degradeable capsule containing a pharmaceutical or consumable or other substance, for example a detergent. The capsules may contain solid or liquid substances. Blow moulding apparatus suitable for forming such capsules is also disclosed and claimed

Description

Method and apparatus for blow molding polyvinyl alcohol capsules and capsules blow molded polyvinyl alcohol.

The present invention relates to capsules, particularly biodegradable capsules, and devices and methods to form such capsules.

There is a demand for biodegradable capsules. Such capsules may contain substances that, during biodegradation or solubilization of the capsule walls, it free. The release rate of the substance can controlled, for example, by varying the wall thickness of the capsule. The demand for such capsules is particularly pronounced in relation to consumable capsules containing example, pharmaceutical substances or dietary supplements Vitamins or minerals.

The use of gelatin to form such is known. capsules to contain liquids. However, it currently exists a significant and growing demand for an alternative or a Jelly substitute. This demand arises particularly in Pharmaceutical applications of patients who are intolerant of jelly. It is desirable to have an alternative source of material for form such capsules. Another problem with gelatin capsules is that they are generally not suitable for containing dry substances or powder

A suitable substitute for a gelatin capsule must not only be biodegradable, in certain applications it must be edible and taste harmless, and of course it must be easily formed as capsules. The potential market for a suitable substitute for gelatin is important and several alternatives have been tried over many years, but all have different disadvantages. Two-part capsules are also known; These may pose different restrictions to the properties of the material and are generally only suitable for containing powdered or dried substances. They are less suitable for containing liquids and the construction in two parts can lead to complications in the formation and filling and / or it can mean that the contents are not hermetically
sealed.

US-A-2,897,854 describes a method for forming filled capsules comprising form a resin shell, preferably using gelatin, and fill and expand the envelope using pressure from a Filling material.

US-A-3,159,545 describes a method to safely retain radioactive material in a capsule filled, preferably with gelatin, comprising suspend or dissolve the radioactive material in an oil or a wax that is solid below body temperature but that melts during ingestion in the body.

WO-A-97/35537 describes a method to encapsulate a substance between two films of an encapsulation material.

JP-A-01022500 describes a method to form a capsule by molding a section upper and lower capsule, filling the lower section of the capsule with powder and resealing the upper sections and Bottom of the capsule.

US-A-4,263,251 describes a method and an apparatus for forming a gelatin capsule in a piece to pack liquid medicines, having the capsule the same conformation and dimensions as a two capsule pieces.

FR-A-2724388 describes a blow molded biodegradable PVA container, for example a bottle, to contain harmful substances.

The invention seeks a general objective provide a viable alternative to gelatin capsules. Aspects of the invention are indicated in the claims. independent and preferred features are indicated in the dependent claims.

In a first aspect, claim 1 of the invention defines a capsule having walls formed by molding by injection blowing a composition containing PVA and which It contains a consumable substance, where the PVA composition comprises up to 20% by weight of a plasticizer, an acid amide C 12 to C 24 straight or branched chain fatty as a lubricant and an inert or consumable load.

PVA has not been commercially manufactured until now as capsules containing a substance due to the Well known and established conventional properties of PVA. However, the inventor has found that using a PVA composition provided as a feedstock of polymer in the form of a compressed tablet or tablet cold, training can be achieved as a result surprisingly reliable of items such as capsules and so the PVA can be surprisingly used satisfactorily in this new app.

The capsule is most preferably sealed; This can prevent the deterioration of the substance. The substance It can be consumable. Particularly, if the substance is consumable, the PVA composition may contain exclusively food grade ingredients. The composition of PVA can contain a load that is inert or consumable, for example calcium carbonate and / or a product derived from plants or vegetables, such as wood flour or rice husk.

The substance can be substantially solid, dry or powdered The invention is particularly useful for facilitate the supply of a sealed capsule (one part, substantially unitary) that contains a solid substance. Until now, it has not been practical to supply powdered substances encapsulated in large-scale sealed capsules and the invention It may surprisingly facilitate this.

The invention is particularly advantageous when It applies to small capsules, for example that have a volume of less than about 5 cm3, more typically less than about 1 cm3, often about 0.5 cm3.

In a preferred embodiment, the invention provides a sealed blow molded capsule from a PVA composition that contains exclusively ingredients from Food grade and containing a consumable substance.

As noted above, the capsule is shape by injection blow molding; this provides a surprisingly convenient means to form reliably capsules Historically, PVA applications have been limited due to difficulties encountered to extrude it in state molten: namely, that the molten extruded PVA becomes very unstable and significant residues adhere to the apparatus of extrusion; that very careful control of the processing conditions and specialized devices; and that procedure has to be cut and the device purged frequently. Due to this lack of reliability, the PVA has not generally considered a suitable candidate for molding by blown in general, since irregularities can lead to movie break. In a relatively small capsule and delicate that may need to contain an exact amount measure of substance, such problems would be even more intense. Without Surprisingly, however, if the PVA has been combined and pressed into cold as described here, it can be extruded in molten state reliably in a blow molding apparatus, such as the described here, to form capsules. These compositions can have mechanical properties similar to gelatin and can be Edible, having a harmless taste. These compositions they can thus be used successfully to replace the jelly.

Apart from choosing a suitable material, there are several problems associated with blow molding to a high quality standard in an economical way. Extrusion blow molding is a technique that is normally used to mold hollow plastic items such as bottles from thermoforming polymers. Conventionally, the thermoformable polymer is hot extruded first in a preform or parison. Next, a two-part molding die is closed around the preform. If the thermoformable polymer is too viscous for this to be feasible, the two part molding matrix is closed first and the hot extruded thermoformable polymer is injected into it. Air is injected into the preform to expand the preform against the mold cavity. The preform is thus blow molded into the conformation of the die cavity. The mold is then opened / separated and the blow molded article is removed. One of the problems is the minimization of the cycle time to produce a molded article. Modalities of the present invention provide an apparatus that includes a molding device that allows injection blow molding of a PVA composition to a reliable standard while minimizing the time of the
cycle.

Claim 12 of the present invention provides an apparatus for forming a sealed filled capsule that It has walls formed from a composition of PVA, apparatus which includes:

a hopper of supply containing a supply of combined PVA tablets cold pressed comprising a composition of PVA, where The PVA composition comprises up to 20% by weight of a plasticizer, a C12 to C24 fatty acid amide of linear or branched chain as a lubricant and an inert load or consumable;

means for extrude the pressed cold pads in molten state to form the PVA feed for blow molding;

means that define a plurality of molding cavities;

means for inject a source of PVA composition into each cavity of molding;

means for inflate the composition of PVA in each molding cavity to form a blow molded capsule;

means for fill each capsule with a consumable substance;

means for seal each capsule; Y

means for Eject the filled capsule.

According to claim 13, provides a procedure to form a filled capsule, which understands:

receive a supply of combined cold pressed PVA tablets (10) that they comprise a PVA composition, wherein the PVA composition comprises up to 20% by weight of a plasticizer, an acid amide C 12 to C 24 straight or branched chain fatty as a lubricant and an inert or consumable load;

extrude in molten state the cold pressed pads (12) to form a PVA feed for blow molding;

inject the PVA feed in a mold (30) defining a plurality of cavities;

inflate the PVA inside each mold cavity to form a molded capsule by blowing;

fill in the capsule with a consumable substance (34);

seal the capsule; Y

eject the loaded capsule

The means or mold that define a plurality of mold cavities may comprise a mold formed by separable parts and preferably comprise a mold having two halves. If the mold comprises two halves, each half of the mold contains a series of respective entrances so that, when joined, both halves form a mold comprising a row of cavities suitable to form capsules. If the mold It consists of more than two separate parts, the parts must be such that, when joined together, they form a mold comprising a row of cavities suitable to form capsules. Preferably, The mold has at least about 10 cavities. Mold may have more, for example about 20 or about  30, cavities in a row. Typically the cavities will form capsules having a volume of less than 5 cm3, plus typically less than about 1 cm3, often about 0.5 cm3. Typically, the procedure involves bring the parts (halves) of the mold into contact, inject the Composition of hot-extruded PVA in each mold, inflate the PVA composition in each mold to form a capsule, fill Each capsule with a substance and seal each filled capsule.

The use of the molding device of the present invention, that is the means defining a row of cavities molding, allows injection, inflation, filling and successive sealing of a number of capsules with a single act of join the parts (of the mold) with each other and an act of separation of the mold halves, thus minimizing the number of times that parts (halves) of the mold have to contact each other and separated by forming a filled capsule. Thus, the time of cycle to produce a molded article is minimized. At method of the present invention, it is preferred that the step of filling is carried out so that the capsules are filled in quick succession. This can ensure consistent items of capsules For pharmaceutical applications in particular, the consistency and accuracy of the amount of filling measured is very important. Preferably, the PVA injection stage is carried to out for all cavities in rapid succession, for example moving the mold with respect to an injection source, or shape substantially simultaneous.

The apparatus may comprise stations physically separated for some or all of the stages of injection, inflation, filling and sealing. The device too may comprise translation means to move the mold of a Station to another.

A fluid, usually a gas, pressurized Suitable can be used to inflate the PVA composition. Usually, such means use compressed air. In a preferred embodiment of the present invention, an inert gas is used such as nitrogen or argon to inflate the PVA composition. The capsule then contains a substantially inert atmosphere before filling with the substance. This has the advantage of minimize exposure of the substance to air. This is from Particular importance for substances that are sensitive to air and / or that oxidize easily.

An injection nozzle can be used to refill the capsule The capsule can be filled with a substance It may be in the form of a liquid or a powder. Previously, it they generally used gelatin capsules to contain only liquids and powdered medications were contained in capsules of two parts. Therefore, another surprising advantage of this invention is that it produces a sealed capsule, substantially of one part, which is suitable for containing dust. One capsules Part are more air tight than two-part capsules. One-part capsules are better for applications of controlled release since the thickness of the capsule walls It is more uniform.

Although the capsules of the present invention are suitable for pharmaceutical applications, for example to contain pharmaceutical substances such as medicaments, and suitable for containing dietary supplements such as vitamins, minerals and edible oils, they can also be used in other applications that require release (controlled ) of a substance by means of biodegradation or solubilization of a wall of a
capsule.

Preferably, the sealing is done by middle of a blade. Preferably, the blade is heated and is passed over the top of the capsule sealing that mode the top of it. The molding device is such that more than one capsule can be sealed by the same through feed of the blade. Therefore, this is a particularly Fast, clean and effective to seal the capsules. This method of sealing helps minimize exposure of the substance contained in the air capsule. This is particularly important for substances that are sensitive to air and / or oxidize easily. The parts (halves) of the mold are then separated and the capsules Stuffed are released.

Additional aspects and features Preferred are indicated in the claims.

An embodiment of the invention will be described. now, by way of example only, with reference to the drawings Attachments, in which:

Figure 1 is a schematic diagram generalization of an apparatus according to a modality of the invention;

Figure 2 shows a front view schematic of a capsule-forming cavity;

Figure 3 shows a side view schematic of a capsule-forming cavity showing the opposite mold halves;

Figure 4 shows a front view of a blow molding apparatus having a plurality of cavities molding;

Figure 5 shows a section through the apparatus of Fig. 4.

In the figures, similar parts are indicated by similar reference numbers.

Referring to Fig. 1, a supply of material 1 for feeding PVA tablets to through a supply hopper 10 (or other device of proper administration) to a melt extruder 12 which It can comprise a screw type extruder like the one used typically to extrude conventional thermoplastics, whose output It is supplied to a blow molder 14. Blow molding it has a plurality of cavities 15 of molding, which have to be described further below, in which they are formed capsules and receives a supply of 16 compressed gas and a supply of a substance to be encapsulated 2 through a dosing device 18. In the mode shown, the substance is a pharmaceutical product, but others can be used substances, for example detergents. Although the device is shown as separate parts, the functions can be integrated, in particular the function of the dosing apparatus is conveniently integrated in the blow molder portion It fills the capsules. The blow molder ejects the 22 capsules filled to a suitable container 20.

In reference to Figs. 2 and 3, a mold 30 formed of halves 30a, 30b of the opposite mold provides a plurality of cavities in the conformation of the desired capsule. A single ellipsoidal cavity 15 is shown in Fig. 2. It can form a more complex conformation and this can incorporate a logo for example. A thin wall of PVA composition 31 it is formed inside the mold cavity from a current 36 injected with PVA derived from melt extruder 12. Although in some cases the polymer can be injected directly in the cavity, more preferably, a preformed section of polymer, typically tubular, is extruded and this section is trapped between opposite mold halves, sealing one end the closure of the mold halves. The capsule is inflated by means of compressed gas injected through the nozzle 32 opposite the trapped end so that it fills the cavity and the substance liquid or powder to fill the capsule can be injected by middle of a needle 34. The needle must be of sufficient diameter to  allow the liquid to flow under viscosity conditions and expected liquid pressure. Similarly, for substances in powder, the diameter should be sufficient to avoid clogging. Such considerations are well known to experts in the medicine capsule filling technique and it will be appreciated that problems can be alleviated by increasing the injection hole or increased injection pressures, or reducing the size of particle or viscosity, for example processing solids or adding diluents to liquids.

After the injection of the substance, the Needle is removed and the capsule is preferably sealed. If he polymer is sufficiently molten and the needle is sufficiently Small, the capsule can self seal. More preferably, for ensure reliable sealing, a heated blade or other utensil is passed through the capsule in the region of the needle opening to cause fusion and sealing capsule premises. The excess not cut directly by the action of the mold halves that are put in contact or by the Sealing blade can be trimmed, although normally A burr will remain. A visible burr can provide a certainty that the integrity of the capsule remains and this can be useful in the case of a pharmaceutical or consumable capsule and can be provided for decorative or advertising purposes at other cases. The invention independently provides a capsule. sealed, particularly a pharmaceutical product, formed from PVA, which contains a substance and has a burr.

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producción de cápsulas que puede alcanzarse.}

Figs. 4 and 5 show an example of a practical mold that embodies the principles shown in the schematic figures. This example shows a single needle device 39 used to inject polymer, air and substance. A row of needle devices can be used to fill a row of capsules simultaneously or a single-needle device, or a smaller number of needle devices, can be used to fill only a proportion of the cavities and move relative to the mold to complete the filling procedure of all cavities. The substance can be injected by means of a needle separated from the device that supplies the polymer. Not shown, the mold is preferably provided with cooling to ensure faster solidification of the injected polymer. Multiple rows of multiple capsules can be supplied from a single extruder; as will be appreciated, the higher the number of molding cavities,

 \ hbox {the faster the speed of
capsule production that can be achieved.} 

The composition containing PVA used for form the feeding material 1 in the modalities is in the form of cold pressed tablets or tablets and comprises a combination of PVA as defined in claim 1. The resulting combination is suitable for extrusion in apparatus of conventional melt extrusion. The composition has typically a flexural modulus similar to other polymers extrudable Known advantageous properties of PVA, such as high tensile strength, good puncture resistance and good barrier characteristics, are retained in this composition.

The feeding material comprises a composition containing PVA comprising up to 20%, especially 5 to 15%, plasticizer and up to 5%, especially 0.5 to 2.5% by weight of lubricant.

In embodiments of the invention, they have been obtained compositions containing extrudable and blow moldable PVA comprising fully hydrolyzed PVA as well as PVA partially hydrolyzed, and that include PVA that is 70% or more hydrolyzed

Compositions containing PVA may have a molecular weight of the PVA that varies from about 20,000, in some cases of around 10,000, up to more than 150,000. Generally, the application of the present invention is not limited to PVA of no particular hydrolysis percentage or of any weight particular molecular.

The lubricating composition of the invention is provides in order to improve the thermal instability of the composition under extrusion. The lubricant can be called internal lubricant, since its function is to improve lubrication between the polymer chains.

The compositions of the invention may be intended for consumption and hence the lubricant is approved for this purpose The lubricant is a fatty acid amide C 12 -C 22 straight or branched chain, more particularly C 16 {C 20}. Are obtained particularly and surprisingly good results if the lubricant comprises stearamide, a C18 fatty acid amide linear chain

The compositions of the invention include also typically a plasticizer, to decrease the temperature of fusion of the polymer under extrusion. The plasticizer can properly selected from glycerin, ethylene glycol, triethylene glycol, low molecular weight polyethylene glycols and amides Low molecular weight. A particularly preferred plasticizer comprises or consists of glycerol.

Although the proportion of components present may vary in the compositions of the invention, embodiments of the invention generally comprises, by weight, up to 50% load and Up to 5% lubricant. More particular modalities of the invention comprise, by weight, 5-50% load, 40-80% PVA, up to 5% lubricant and 5-20% plasticizer.

Good results have been obtained with modalities that have the following constitution, by weight:

(to)

from 40 to 80% PVA;

(b)

of 5 at 50% load;

(C)

of 5 at 15% plasticizer, preferably glycerol;

(d)

from 0.5 to 2.5% C 12 -C 24 fatty acid amide as an internal lubricant, most preferably Octodecanamide

Results have been obtained particularly good in embodiments of the invention that have the following constitution, by weight:

(to)

from 40 to 70% PVA;

(b)

from 20 to 50% charge, preferably an inorganic material micronized such as talc, preferably coated with stearate;

(C)

Out of 8 at 15% plasticizer, preferably glycerol;

(d)

from 0.5 to 1.5% C12-C24 fatty acid amide as an internal lubricant, most preferably octodecanamide; Y

(and)

from 0.0001 to 0.1% external lubricant, preferably Stearate

The composition may contain residual moisture, enough to allow the composition to clump together as a cold pressed tablet.

Exemplary compositions will now be detailed that They can be used for the feeding material.

Example 1

A combination of, by weight, approximately 60% of fully hydrolyzed PVA, 30% calcium carbonate, 10% glycerol, 0.01% zinc stearate and 1% octadecanamide are Prepared in a high speed mixer. It was found that he had a white / cream color with the following properties:

       \ vskip1.000000 \ baselineskip
    

density 1.65 g / cm3 density in state molten 1.46 g / cm3 at 200 ° C (low ISO 1183) MFR 357 (10 minutes / 200 ° C / 21.6 kilograms, low ISO 1133) Temperature of fusion 200 ° C Temperature of processing 190-200 ° C weather of permanence up to 15 minutes time of dried out 4 hours at 80 ° C

       \ vskip1.000000 \ baselineskip
    

Example 2

A combination was prepared in a similar manner. to example 1 of, by weight, approximately 60% PVA partially hydrolyzate, 30% calcium carbonate, 10% glycerol, 0.01% zinc stearate and 1% octadecanamide. It was found that he had the following properties:

       \ vskip1.000000 \ baselineskip
    

density 1.65 g / cm3 density in state molten 1.38-1.40 g / cm3 at 190 ° C (low ISO 1183) MFR 22 (10 minutes / 190 ° C / 5 kilograms, low ISO 1133) apparent viscosity in state molten 236/49 (Pa.s 1,000 s / 10,000 s) Temperature of fusion 200 ° C Temperature of processing 190-200 ° C weather of permanence up to 15 minutes time of dried out 4 hours at 80 ° C

       \ vskip1.000000 \ baselineskip
    

The compositions of examples 1 and 2 they were extruded and blow molded successfully.

Example 3

Compositions containing PVA of Examples 1 and 2 were examined regarding their ability to extrusion in injection molding machines made by Brabender, Killion, Windsor, Hesas, Battenfield, Fischer, Demag and Arburg Extrusion processing was carried out using a single full feed screw with constant pitch. The temperature of cylinder had a profile of 180-200 ° C (molten mass 190-210 ° C) and screw speed varied typically between 20 and 120 rpm. The cutting of the device was carried out maintaining the temperature for up to 15 minutes with rotation of the screw stopped, for a period of 3 hours reducing the temperature up to 100 ° C with screw rotation stopped and subsequently completing the stop by disconnecting the machine.

If a composition is extrudable or not (so It is understood in common extrusion apparatus) it will be clear usually for one skilled in the art. In case it is require a test, however, it is suggested that the ability to extrusion is determined by attempting extrusion in one or more of the machines of the manufacturers named above using a single full feed screw with constant pitch with speeds and temperatures in the previous interval. If the composition is extruded reliably on at least two of the previous machines with adjustment of usual parameters, it must be considered extrudable; if they are obtained constant problems and extrusion is only possible under highly specific conditions with a specialized team, must Consider that it is not extrudable.

Examples 4-9

Compositions containing PVA were prepared as combinations of the following components in quantities shown:

one

As regards the extrusion apparatus, it is advantageous to use chrome coated screws and for the path of melt flow use surfaces deposited with chromium and gradual conical pieces to streamline the melt.

As an alternative to calcium stearate as a charge, organic substances such as shell can be used of rice and wood flour.

Modalities of the invention thus provide capsules formed from compositions containing PVA that They are biodegradable.

Aspects of the invention can provide furthermore independently or in combination any one or more of the preferred or optional features described here and / or one any or more of (i) the use of a PVA composition in the manufacture of a capsule; (ii) a PVA capsule molded by sealed blow containing a powder substance; (iii) one pharmaceutical composition contained within a PVA capsule; (iv) a method for sealing a blow molded PVA capsule which contains a substance, which comprises melting a portion of the capsule; and (v) the use of PVA in the manufacture of a capsule consumable that contains a medication for the treatment of a been in a patient with aversion to the consumption of gelatin. In preferred applications, particularly pharmaceuticals and food supplements, the composition of PVA is preferably soluble in cold water. In dispenser applications of detergents, the solubility temperature can be selected for provide controlled or delayed release. In certain applications, for example paintball capsules, can use PVA soluble in hot water.

The reference numbers that appear in the claims will not have a limiting effect.

Claims (13)

1. A blow molded capsule with injection that has walls formed from a composition that  it contains PVA and they contain a consumable substance, where the PVA composition comprises up to 20% by weight of a plasticizer, a straight chain C 12 to C 24 fatty acid amide or branched as a lubricant and an inert or consumable load. 2. A capsule according to claim 1, wherein the PVA composition comprises partially PVA hydrolyzate having a molecular weight of at least about 10,000 3. A capsule according to claim 2, in which the charge comprises calcium carbonate. 4. A capsule according to claim 2 or 3, in which the plasticizer comprises glycerol. 5. One capsule according to any of the claims 2 to 4, wherein the fatty acid amide comprises a C 16 to C 20 fatty acid amide. 6. A capsule according to claim 5, wherein the fatty acid amide comprises stearamide. 7. One capsule according to any of the claims 2 to 6, wherein the PVA composition comprises also stearate as an external lubricant. 8. One capsule according to any preceding claim, wherein the capsule is sealed. 9. One capsule according to any preceding claim, wherein the capsule is consumable and in which the PVA composition contains exclusively ingredients from Food quality. 10. One capsule according to any preceding claim, wherein the capsule has a volume of 5 cubic centimeters or less. 11. One capsule according to any preceding claim, wherein the capsule contains a dose Measurement of a pharmaceutical substance. 12. An apparatus for forming a filled capsule sealed that has walls formed from a composition of PVA, apparatus comprising:

a hopper (10) of supply containing a supply of PVA tablets (1) cold pressed combinations comprising a PVA composition, wherein the PVA composition comprises up to 20% by weight of a plasticizer, a C12 to C24 fatty acid amide of linear or branched chain as a lubricant and an inert load or consumable;

means for Extrude in the molten state (12) the cold pressed pads for form the PVA feed for blow molding;

means that define a plurality of mold cavities (30);

means for inject a source of composition (36) of PVA into each cavity (15) molding;

means for inflate (32) the PVA composition in each molding cavity to form a blow molded capsule;

means for fill each capsule with a consumable substance (34);

means for seal each capsule; Y

means for Eject the filled capsule.

13. A procedure to form a capsule fills, comprising:

receive a supply of combined cold pressed PVA tablets (1) that they comprise a PVA composition, wherein the PVA composition comprises up to 26% by weight of a plasticizer, an acid amide C 12 to C 24 straight or branched chain fatty as a lubricant and an inert or consumable load;

extrude in molten state the cold pressed pads (12) to form a PVA feed for blow molding;

inject the PVA feed in a mold (30) defining a plurality of cavities (15);

inflate the PVA inside each mold cavity to form a molded capsule by blowing;

fill in the capsule with a consumable substance (34);

seal the capsule; Y

eject the loaded capsule